Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter

Prisca S. Leferink; Nicole Breeuwsma; Marianna Bugiani; Marjo S. van der Knaap; Vivi M. Heine

doi:10.1002/glia.23289

Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter

Prisca S. Leferink, Nicole Breeuwsma, Marianna Bugiani, Marjo S. van der Knaap, Vivi M. Heine^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Leukodystrophies are often devastating diseases, presented with progressive clinical signs as spasticity, ataxia and cognitive decline, and lack proper treatment options. New therapy strategies for leukodystrophies mostly focus on oligodendrocyte replacement to rescue lack of myelin in the brain, even though disease pathology also often involves other glial cells and the spinal cord. In this study we investigated spinal cord pathology in a mouse model for Vanishing White Matter disease (VWM) and show that astrocytes in the white matter are severely affected. Astrocyte pathology starts postnatally in the sensory tracts, followed by changes in the astrocytic populations in the motor tracts. Studies in post-mortem tissue of two VWM patients, a 13-year-old boy and a 6-year-old girl, confirmed astrocyte abnormalities in the spinal cord. For proper development of new treatment options for VWM and, possibly, other leukodystrophies, future studies should investigate spinal cord involvement.

Original language	English
Pages (from-to)	862-873
Number of pages	12
Journal	Glia
Volume	66
Issue number	4
Early online date	27 Dec 2017
DOIs	https://doi.org/10.1002/glia.23289
Publication status	Published - Apr 2018

Funding

ZonMw VIDI, research grant, Grant Number: 91712343; E-Rare Joint Call project, Grant Number: 9003037601; European Leukodystrophy Association (ELA) Research Grant, Grant Number: 2014-012L1; NWO Spinoza award. V. M. H. is supported by a ZonMw VIDI research grant (91712343), and E-Rare Joint Call project (9003037601), and an European Leukodystrophy Association (ELA) Research Grant (2014-012L1). M. S. v. d. K. and V. M. H. are supported by the NWO Spinoza award. We thank Marjolein Breur for performing the immunohistochemistry on the human tissue. We thank Matt Clancy for his help in the design of the schematic representation of the spinal cord in Figure 3c. We thank H. H. Tsai for her constructive feedback on glial cell markers in the spinal cord.

Funders	Funder number
ZonMw	91712343, 9003037601
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Association Européenne contre les Leucodystrophies	2014-012L1

Keywords

astrocytes
leukoencephalopathy
neuroglia
neuropathology
spinal cord
vanishing white matter disease

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/glia.23289

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abstract = "Leukodystrophies are often devastating diseases, presented with progressive clinical signs as spasticity, ataxia and cognitive decline, and lack proper treatment options. New therapy strategies for leukodystrophies mostly focus on oligodendrocyte replacement to rescue lack of myelin in the brain, even though disease pathology also often involves other glial cells and the spinal cord. In this study we investigated spinal cord pathology in a mouse model for Vanishing White Matter disease (VWM) and show that astrocytes in the white matter are severely affected. Astrocyte pathology starts postnatally in the sensory tracts, followed by changes in the astrocytic populations in the motor tracts. Studies in post-mortem tissue of two VWM patients, a 13-year-old boy and a 6-year-old girl, confirmed astrocyte abnormalities in the spinal cord. For proper development of new treatment options for VWM and, possibly, other leukodystrophies, future studies should investigate spinal cord involvement.",

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AU - Heine, Vivi M.

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N2 - Leukodystrophies are often devastating diseases, presented with progressive clinical signs as spasticity, ataxia and cognitive decline, and lack proper treatment options. New therapy strategies for leukodystrophies mostly focus on oligodendrocyte replacement to rescue lack of myelin in the brain, even though disease pathology also often involves other glial cells and the spinal cord. In this study we investigated spinal cord pathology in a mouse model for Vanishing White Matter disease (VWM) and show that astrocytes in the white matter are severely affected. Astrocyte pathology starts postnatally in the sensory tracts, followed by changes in the astrocytic populations in the motor tracts. Studies in post-mortem tissue of two VWM patients, a 13-year-old boy and a 6-year-old girl, confirmed astrocyte abnormalities in the spinal cord. For proper development of new treatment options for VWM and, possibly, other leukodystrophies, future studies should investigate spinal cord involvement.

AB - Leukodystrophies are often devastating diseases, presented with progressive clinical signs as spasticity, ataxia and cognitive decline, and lack proper treatment options. New therapy strategies for leukodystrophies mostly focus on oligodendrocyte replacement to rescue lack of myelin in the brain, even though disease pathology also often involves other glial cells and the spinal cord. In this study we investigated spinal cord pathology in a mouse model for Vanishing White Matter disease (VWM) and show that astrocytes in the white matter are severely affected. Astrocyte pathology starts postnatally in the sensory tracts, followed by changes in the astrocytic populations in the motor tracts. Studies in post-mortem tissue of two VWM patients, a 13-year-old boy and a 6-year-old girl, confirmed astrocyte abnormalities in the spinal cord. For proper development of new treatment options for VWM and, possibly, other leukodystrophies, future studies should investigate spinal cord involvement.

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Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter

Abstract

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Keywords

UN SDGs

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